Abstract
Perturbations of the colonic microbiota can contribute to the initiation and progression of colorectal cancer, leading to an increase in pathogenic bacteria at the expense of protective bacteria. This can contribute to disease through increasing carcinogenic metabolite/toxin production, inducing inflammation, and activating oncogenic signaling. To limit disease progression, external factors that may influence the colonic microbiota need to be considered in patients with colorectal cancer. One major factor that can influence the colonic microbiota is iron. Iron is an essential micronutrient that is required by both prokaryotes and eukaryotes for cellular function. Most pathogenic bacteria have heightened iron acquisition mechanisms and therefore tend to outcompete protective bacteria for free iron. Colorectal cancer patients often present with anemia due to iron deficiency, and thus they require iron therapy. Depending upon the route of administration, iron therapy has the potential to contribute to a procarciongenic microbiota. Orally administered iron is the common treatment for anemia in these patients but can lead to an increased gut iron concentration. This suggests the need to reassess the route of iron therapy in these patients. Currently, this has only been assessed in murine studies, with human trials being necessary to unravel the potential microbial outcomes of iron therapy.
Highlights
The gut microbiota comprises an intricate population of microorganisms, which exert a complex relationship with their host during both homeostasis and disease
Dysbiosis can cause an increase in pathogenic bacteria at the expense of protective bacteria, which can contribute to both colitis and cancer
Most bacteria require iron for growth and survival, many pathogenic bacteria have highly specialized iron-acquiring mechanisms that aid in their virulence. This has been supported in studies showing that higher luminal iron concentration leads to a greater abundance of pathogenic bacteria, while a decrease in gut iron hinders pathogenic bacterial growth and favors protective bacterial species
Summary
The gut microbiota comprises an intricate population of microorganisms, which exert a complex relationship with their host during both homeostasis and disease. Numerous gastrointestinal diseases, including colorectal cancer, are associated with changes in gut microbiota compared to healthy controls [1] These perturbations, often referred to as dysbiosis, may have a role in contributing to disease mechanisms associated with colitis, tumor initiation, and tumor progression [2,3]. Increased colonic iron concentration through iron supplementation has been shown to promote pathogenic bacterial species in iron-deficient Kenyan infants while decreasing protective bacteria such as Bifidobacteria and lactobacillus. This supports the role of increased luminal iron promoting pathogenic bacteria at the expense of beneficial bacteria, the underlying mechanisms are not fully understood [12,13]. The relationship between the microbiota and colorectal cancer will be discussed in this review, focusing on how iron can alter bacterial populations and the outcomes of iron supplementation
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